Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors (AGIs) are a class of oral antidiabetic agents primarily used in the management of type 2 diabetes mellitus. They work by delaying the absorption of carbohydrates in the small intestine, thereby reducing postprandial (after-meal) blood glucose spikes. Unlike other antidiabetic medications, they do not stimulate insulin release but act locally within the gastrointestinal tract.

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Mechanism of Action

• The enzyme alpha-glucosidase, located in the brush border of the small intestine, breaks down complex carbohydrates and disaccharides (e.g., starch, sucrose) into absorbable monosaccharides such as glucose.

• Alpha-glucosidase inhibitors (such as acarbose and miglitol) competitively inhibit this enzyme, leading to:

  • Delayed carbohydrate digestion

  • Reduced and slower glucose absorption

  • Lower postprandial hyperglycemia

• Since they do not directly affect insulin secretion, they have a low risk of hypoglycemia when used as monotherapy.

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Therapeutic Uses

1. Type 2 Diabetes Mellitus

   • Used as monotherapy in patients with mild to moderate hyperglycemia, particularly with elevated postprandial glucose levels.

   • Commonly prescribed in combination with other antidiabetic drugs (metformin, sulfonylureas, insulin, or thiazolidinediones) for better glycemic control.

2. Prediabetes / Impaired Glucose Tolerance

   • Can delay the progression from impaired glucose tolerance to type 2 diabetes in high-risk individuals.

3. Polycystic Ovary Syndrome (PCOS) (off-label)

   • Occasionally used to improve insulin sensitivity.

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Common Agents and Doses

1. Acarbose

   • Usual dose: 25–100 mg orally, three times daily with the first bite of each main meal.

   • Maximum dose: 300 mg/day.

2. Miglitol

   • Usual dose: 25–100 mg orally, three times daily with meals.

   • Unlike acarbose, miglitol is absorbed systemically but still acts mainly in the intestine.

3. Voglibose (widely used in Asia, not FDA-approved in the US)

   • Dose: 0.2–0.3 mg orally, three times daily with meals.

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Contraindications

• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease)

• Intestinal obstruction or chronic intestinal disorders

• Severe renal impairment (particularly for miglitol)

• Hypersensitivity to the drug

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Side Effects

Mostly gastrointestinal due to undigested carbohydrates fermenting in the colon:

• Flatulence

• Abdominal bloating

• Diarrhea

• Abdominal pain

• Rare: hepatotoxicity (with high doses of acarbose)

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Precautions

• Start with a low dose and titrate slowly to minimize gastrointestinal side effects.

• Monitor liver function tests periodically with long-term acarbose use.

• Should be taken with the first mouthful of food to be effective.

• Hypoglycemia can occur if combined with insulin or sulfonylureas; in such cases, treat with oral glucose (dextrose), not sucrose (table sugar), since sucrose breakdown is inhibited.

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Drug Interactions

• Digestive enzyme supplements (e.g., amylase, pancreatin) may reduce efficacy.

• Intestinal adsorbents (e.g., charcoal) can interfere with drug action.

• Can enhance hypoglycemic risk when used with sulfonylureas, insulin, or meglitinides.

• May reduce bioavailability of certain drugs (digoxin with acarbose).